Hereditary Spastic Paraplegia (HSP) has a worldwide prevalence between 1-18 in 100,0001-3 and is characterized by central motor system deficits leading to lower limb spastic paraperesis.4-6 This is due to a “dying back” phenomenon whereby upper motor neurons degenerate progressively, commencing with the longest axons.7,8 HSP can be classified into pure and complicated forms.6 In pure HSP, lower limb spasticity is the only major presenting symptom. Alternatively, in complicated HSP, this spasticity can be accompanied by other neurological or non-neurological symptoms such as ataxia, dementia, mental retardation, deafness, epilepsy, ichthyosis, retinopathy, ocular neuropathy and extrapyramidal disturbances.6,9 There is clinical heterogeneity within families, where age of onset and severity can differ markedly; between families that map to the same locus; and certainly between families which map to separate loci. This complicates genotype-phenotype correlations for HSP.
HSP is also extremely genetically heterogeneous. Eleven genes have been identified out of over 30 loci mapped (SPG1-33). This disease can be transmitted in a dominant (13 loci), a recessive (15 loci) or an X-linked manner (4 loci).9-11 By far the most common locus for the disease is SPG4, with mutations in the microtubule severing protein spastin accounting for ˜40 percent of dominant HSP cases (MIM604277).12,13 
SPG8 is a pure form of hereditary spastic paraplegia with relatively little interfamilial variability in phenotype. SPG8 is considered to be one of the more aggressive subtypes of HSP with disease onset occurring for patients as early as their 20 s or 30 s. It was first identified in a Caucasian family as a 6.2 cM region between the markers D8S1804 and D8S1774.14 The family contained 15 patients affected with spasticity, hyperreflexia, extensor plantar reflexes, lower limb weakness, decreased vibration sensation and limited muscle wasting. The candidate region was further reduced to 3.4 cM due to a lower recombinant in a second family, narrowing the interval between markers D8S1804 and D8S1179.15 This family as well as a third Brazilian family linked to SPG8 also presented with pure adult onset HSP.16 For two of the families, a muscle biopsy was performed;14,16 however, no gross histological or histochemical abnormalities were observed. Ragged red fibers have been observed in muscle biopsies of HSP patients with paraplegin mutations.17 These three families thus present with relatively severe, pure spastic paraplegia.
HSP is one of the most genetically heterogeneous diseases, caused by mutations in at least 31 different genes. This means that >0.1% of genes in the human genome can be mutated resulting in one predominant neurological outcome: the degeneration of upper motor neuron axons. This heterogeneity may in part explain why it was originally difficult to identify the eighth HSP locus, SPG8 leading to an expansion of the candidate interval. The eighth HSP locus, SPG8, is on chromosome 8p24.13. It is possible that two spastic paraplegia genes exist on chromosome 8q23-24, and the overlap of linkage results from both loci yielded a region between the two causative genes. This is similar to the SPG33 gene ZFVE27 which is in close proximity to the SPG9 (MIM 601162) and SPG27 (MIM609041) loci.25 Alternatively, one originally reported family may have had a false positive linkage result to chromosome 8.
The present description refers to a number of documents, the content of which is herein incorporated by reference in their entirety.